A large number of proteins of diverse origin and biological function are known to contain covalently-linked carbohydrate and are designated as glycoproteins. Among these plasma proteins, enzymes, hormones, mucins, collagens, basement membranes and components of cellular membranes may be listed. Recently there have been indications that information vital to physiological processes may be coded in the saccharide sequences of glycoproteins and that when these molecules are located on the surface of the cell they participate in the interaction of cells with each other and with macromolecules in the environment. Furthermore glycoproteins abnormalities are believed to exist in a number of pathological conditions ranging from cancer to diabetic microangiopathy. This renewal application is being submitted to make possible studies on the structure of a number of biologically important glycoproteins from mammalian tissues to provide insight into the function of these molecules in normal and diseased states. Although continued attention will be directed to the soluble glycoproteins of plasma and tissue, including fetuin, thyroglobulin and serum lipoproteins, as well as to the carbohydrate of basement membranes and collagens, a major new direction of research will encompass the glycoproteins of plasma membranes and the membranes of intracellular organelles. Plasma membranes of cells with recognized hormone receptors (namely fat, thyroid and muscle) will be investigated, while intracellular membranes for study will be obtained from the nuclear and mitochondrial envelopes. Chemical and enzymatic techniques will be applied to carefully purified glycoproteins to obtain information about the nature and structure of their carbohydrate units and the location of these on the peptide chains. An evaluation of the biological function of the saccharide portion of membrane glycoproteins will be made by binding studies with radiolabeled hormones and lectins. A study of the glycoprotein subunits of the diabetic renal glomerular basement membrane will be undertaken to provide a basis for understanding the microangiopathy of this disease.